The overall objectives of this research proposal are to investigate the roles of gastrointestinal hormones in the digestive processes. We have available specific radioimmunoassays for gastrin, secretin, gastric inhibitory peptide (GIP), cholecystokinin (CCK), vasoactive intestinal peptide (VIP), glucagon, pancreatic polypeptide (PP) and somatostatin. We have in different stages of development, radioimmunoassays for bombesin, motilin and growth hormones. We will continue our studies to validate these assay systems. These radioimmunoassays will be used to study the temporal pattern of release of gastrointestinal hormones after various stimuli. We continue to study the relationship between the pituitary hormones after various stimuli. We continue to study the relationship between the pituitary hormones on the release of gastrointestinal hormones in normal and hypophysectomized rats and dogs. Similar studies will be performed in normal, hypophysectomized and acromegalic man. We will determine if there are different forms of CCK, secretin, VIP, PP, and GIP in plasma and tissue of man, dog and cats. The pattern of release and tissue levels of different molecular forms of the hormones will be studied in animals, normal man and patients with duodenal ulcer disease (before and after operation). We will continue to study the influence of diseases on the patterns of release of gastrointestinal hormones: specifically, gastrin in Zollinger-Ellison syndrome, VIP in pancreatic cholera and secretin in normal and duodenal ulcer patients. We will correlate biologic activity of gastrointestinal hormones with measurements of their circulating concentrations. We plan to continue to study the mechanisms (organ and cellular) by which gastrointestinal hormones are catabolized. We will study the synthesis of gastrointestinal hormones in cell cultures (ZE tumors, VIP tumors) by incorporation of labeled amino acids into hormones and by radioimmunoassay of culture media. We will investigate the binding of different hormones to target tissue with emphasis upon developing receptor-type assays for gastrointestinal hormones in segments of gastrointestinal mucosa and the ability of different agents to stimulate or inhibit the release of gastrointestinal hormones from segments of the gut.